A study of biochemical markers of selenium status has demonstrated that selenoprotein P and plasma selenium are depressed in patients with cirrhosis, indicating the possibility that the patients are selenium deficient and that selenium supplementation will improve their selenium status. A selenium supplementation study is proposed. Twenty-four patients with Child class C cirrhosis will be recruited and randomized into 3 groups of 8 each. Twenty-four healthy control subjects will be randomized in the same manner. Subjects in the groups will receive, respectively, 200 mug selenium as selenate, 200 mug selenium as selenomethionine, or placebo in a double blind fashion. Supplementation will be continued for 4 weeks with blood sampling weekly. Selenoprotein P and plasma selenium, which are depressed in the patients, will be determined in the blood samples. If both selenium supplements correct the selenoprotein P depression, that result will indicate that the subjects have a relative selenium deficiency that can be corrected by organic or inorganic selenium supplements. If the selenate corrects the depression and the selenomethionine does not, that result will strongly suggest that the transsulfuration pathway in the liver is impaired by the cirrhosis to the extent that selenomethionine cannot be catabolized and release selenide for synthesis of selenoproteins. That result would indicate that inorganic selenium supplements would be necessary and that food selenium would not correct the 6 deficiency. If selenium supplements correct the biochemical selenium deficiency of cirrhosis, a supplementation trial with clinical endpoints would be justified to determine whether patients with cirrhosis would benefit from selenium supplementation. The assays used to measure selenium status in humans are primarily plasma selenoprotein P concentration and glutathione peroxidase activity. These assays can be carried out in our lab but ELISAs are needed to facilitate the performance of these assays in other labs. This proposal includes development of those immunoassays.